Manganese

Neurotoxicity

Administrative data

Endpoint:

neurotoxicity: sub-chronic inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed to good scientific principles

Data source

Reference

Reference Type:

publication

Title:

Bioaccumulation and locomotor effect of manganese dust in rats

Author:

St-Pierre A, Normandin L, Carrier G, Kennedy G, Butterworth R and Zayed J

Year:

2001

Bibliographic source:

Inhal Toxicol 13:623-632

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

3.75 mg Mn/m3 (respirable) exposure 6h/day 5 days/wk for 13 weeks. Blood chemistry + organ weights measured

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Manganese

EC Number:

231-105-1

EC Name:

Manganese

Cas Number:

7439-96-5

Molecular formula:

Mn

IUPAC Name:

manganese

Details on test material:

Metallic Mn (99% pure, Aldrich Chemical Company, Inc., Milwaukee, WI

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Canana Inc. Milwaukee, WI
- Weight at study initiation: 180-200 g
- Fasting period before study: none
- Housing:stainless steel cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22
- Photoperiod (hrs dark / hrs light):12:12

Administration / exposure

Route of administration:

inhalation: dust

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

5 days/wk, 6 h/day.

Doses / concentrations

Remarks:

Doses / Concentrations:
Nominally 3.75 mg/m3
Basis:
other: Air samples were collected in both chambers on a daily basis. Gilian pumps (Gilian Corp., West Caldwell, NJ) with standard three-piece cassettes were used for sampling. The filters were Teflon (manufactured for SKC, Inc., Gelman Sciences, Ann Arbor, MI) w

No. of animals per sex per dose:

26

Control animals:

other: Exposed to 0.004 mg/m3 Mn (respirable)

Examinations

Neurobehavioural examinations performed and frequency:

Following the 13 wks of exposure, locomotor activity was measured using a computerized autotrack system (Columbus Instruments, OH) as
NEUROTOXICOLOGY OF MANGANESE 625 reported by Therrien et al. (1995). The locomotor activity testing included day–night (or light–dark) rhythms and exploratory activity. Animal activity meters were used and installed in a quiet, isolated room with 12-h light/dark cycles. Individual activity profiles for each rat over the 12-h light/dark periods and cumulative activity scores for a period of 36 h were measured as described by Therrien et al. (1995). During this period, food and water were available ad libitum.

Sacrifice and (histo)pathology:

Mn concentrations in organs and blood were determined by INAA. In order to examine in an exploratory way any dysfunction (such as kidney or renal failure) related to Mn exposure, the following biochemical tests were performed by standard techniques: blood hematocrit, blood glucose, blood urea nitrogen (BUN), serum creatinine, bilirubin, transaminases (aspartate aminotransferase, AST; alanine aminotransferase, ALT), alkaline phosphatase, and serum ion

Statistics:

Independent t-test.

Results and discussion

Results of examinations

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

significant decrease of potassium (p < 0.05) and alkaline phosphatase blood concentrations (p < 0.01). Mn concentrations in lung, putamen and cerebellum were significantly higher in E than in C (p < 0.01), as well as in the kidney, frontal cortex, and gl

Behaviour (functional findings):

effects observed, treatment-related

Description (incidence and severity):

Distance travelled during night time was significantly higher (p < 0.01) than during day time for the two nights and for both C and E groups. On the other hand, resting time was significantly higher (p <0.01) during the day for both groups

Applicant's summary and conclusion

Conclusions:

The single concentration of 3.75 mg/m3 respirable Mn appeared to show some effect on locomotor activity in rat. However, no dose-response relationship could be established since only one concentration level was used. Therefore no conclusion can be reached with regards to neurofunctional effects of Mn metal dust via inhalation.